Steric acceleration of intramolecular cyclisations
The promotion of intramolecular cyclisations using various synthetic methodologies
remains an area of considerable interest in organic chemistry. In this thesis, the potential
for large, bulky groups ("steric buttresses") to promote intramolecular cyclisations by a
combination of entropic and enthalpic factors is presented. For the purposes of this study
both Diels-Alder and ene cyclisations have been studied.
The use of steric buttresses to promote the ene cyclisation of a 1,7-diene under relatively
mild conditions is described, with different buttressing groups attached, to enable
comparison of their relative buttressing ability. In this series the thermal stability of the
cyclic products was also investigated, thus allowing further conclusions to be drawn on
the buttressing ability of the groups studied.
The ene reaction of a range of 1,6-dienes to give substituted pyrrolidines was
investigated. This has enabled comparisons to be made on the reactivity of the enophiles
in question. More importantly, the relative buttressing ability of the buttresses studied
has been assesseda, llowing their ability to both promote cyclisation and control
selectivity to be classified. In addition our efforts to develop a viable synthetic route to
kainic acid are discussed.
The thermolysis of 1,6-dienes incorporating a hetero-enophile component was also the
subject of study. The enophiles in this case ranged from carbonyl compounds to their
imino and nitrile counterparts. Once again, this has enabled conclusions to be drawn on
the reactivity of the enophiles involved. In addition, these studies have allowed us to
better understand the suitability of steric buttressing as an aid to intramolecular
Finally, in an effort to develop a chiral steric buttressing methodology, the use of
ß-cyclodextrin ("macrocyclic steric buttressing") to promote an intramolecular Diels-
Alder cyclisation is discussed. This study also resulted in the discovery of a remarkable
solvent effect for an intramolecular, pericyclic reaction.